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1
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Ebrahimi N, Hakimzadeh A, Bozorgmand F, Speed S, Manavi MS, Khorram R, Farahani K, Rezaei-Tazangi F, Mansouri A, Hamblin MR, Aref AR. Role of non-coding RNAs as new therapeutic targets in regulating the EMT and apoptosis in metastatic gastric and colorectal cancers. Cell Cycle 2023; 22:2302-2323. [PMID: 38009668 PMCID: PMC10730205 DOI: 10.1080/15384101.2023.2286804] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 05/11/2023] [Accepted: 08/01/2023] [Indexed: 11/29/2023] Open
Abstract
Colorectal cancer (CRC) and gastric cancer (GC), are the two most common cancers of the gastrointestinal tract, and are serious health concerns worldwide. The discovery of more effective biomarkers for early diagnosis, and improved patient prognosis is important. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can regulate cellular processes such as apoptosis and the epithelial-mesenchymal transition (EMT) leading to progression and resistance of GC and CRC tumors. Moreover these pathways (apoptosis and EMT) may serve as therapeutic targets, to prevent metastasis, and to overcome drug resistance. A subgroup of ncRNAs is common to both GC and CRC tumors, suggesting that they might be used as biomarkers or therapeutic targets. In this review, we highlight some ncRNAs that can regulate EMT and apoptosis as two opposite mechanisms in cancer progression and metastasis in GC and CRC. A better understanding of the biological role of ncRNAs could open up new avenues for the development of personalized treatment plans for GC and CRC patients.
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Affiliation(s)
- Nasim Ebrahimi
- Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran
| | - Ali Hakimzadeh
- Department of Medical Biotechnologies, University of Siena, Tuscany, Italy
| | - Farima Bozorgmand
- Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Sepehr Speed
- Medical Campus, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | | | - Roya Khorram
- Bone and Joint Diseases Research Center, Department of Orthopedic Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kobra Farahani
- Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
| | - Fatemeh Rezaei-Tazangi
- Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Atena Mansouri
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Reza Aref
- Xsphera Biosciences, Translational Medicine group, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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2
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Syllaios A, Sakellariou S, Garmpis N, Sarlani E, Damaskos C, Apostolou K, Kykalos S, Gazouli M, Karavokyros I, Schizas D. The role of miR-101 in esophageal and gastric cancer. Per Med 2021; 18:491-499. [PMID: 34402321 DOI: 10.2217/pme-2021-0024] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
miR-101 is downregulated in various types of cancer, leading to the notion that miR-101 acts as a suppressor in cancer cell progression. The comprehensive mechanisms underlying the effects of miR-101 and the exact role of miR-101 dysregulations in esophagogastric tumors have not been fully elucidated. This review aims to summarize all current knowledge on the association between miR-101 expression and esophagogastric malignancies and to clarify the pathogenetic pathways and the possible prognostic and therapeutic role of miR-101 in those cancer types. miR-101 seems to play crucial role in esophageal and gastric cancer biology and tumorigenesis. It could also be a promising novel diagnostic and therapeutic target, as well as it may serve as a significant predictive biomarker in esophagogastric cancer.
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Affiliation(s)
- Athanasios Syllaios
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Stratigoula Sakellariou
- First Department of Pathology, Medical School, National & Kapodistrian University of Athens, Athens, 11527, Greece
| | - Nikolaos Garmpis
- Second Propedeutic Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Eleni Sarlani
- First Department of Pathology, Medical School, National & Kapodistrian University of Athens, Athens, 11527, Greece
| | - Christos Damaskos
- N.S. Christeas Laboratory of Experimental Surgery & Surgical Research, Medical School, National & Kapodistrian University of Athens, Athens, 11527, Greece
| | - Konstantinos Apostolou
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Stylianos Kykalos
- Second Propedeutic Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Maria Gazouli
- Laboratory of Biology, Medical School, National & Kapodistrian University of Athens, Athens, 11527, Greece
| | - Ioannis Karavokyros
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Dimitrios Schizas
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
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3
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Zhou C, Chen L, Chen R, Xu F, Huang Z, Huang R, Wang W, Xu Q. miR-4486 enhances cisplatin sensitivity of gastric cancer cells by restraining the JAK3/STAT3 signalling pathway. J Chemother 2021; 34:35-44. [PMID: 34167436 DOI: 10.1080/1120009x.2021.1936957] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Along with the occurrence of cisplatin resistance, treatment on gastric cancer (GC) becomes difficult. Therefore, researches on new therapeutic methods to revert cisplatin resistance are becoming increasingly urgent. qRT-PCR was used to quantify the expression of miR-4486, JAK3 in SGC-7901 or SGC-7901/DDP cell lines. WB was utilized to analyze the expression of JAK3, STAT3 and p-STAT3 in SGC-7901/DDP cell lines. CCK-8 assay was used to determine the IC50 of cisplatin on both cell lines and cell viability of SGC-7901/DDP cell lines. The target relationship between miR-4486 and JAK3 was determined by luciferase assay. MiR-4486 expression on apoptosis of SGC-7901/DDP cell lines was determined by flow cytometry. qRT-PCR testified that miR-4486 decreased in SGC-7901/DDP cells, and the expression of miR-4486 mimic increased significantly compared with miR-4486 NC. By CCK-8 assay, the IC50 of cisplatin on both cell lines were 9 μg/mL and 81.3 μg/mL, and overexpression of miR-4486 decreased the viability of SGC-7901/DDP cells. Compared with DDP group, the expression of miR-4486 accelerated SGC-7901/DDP cells apoptosis. Dual-luciferase assay suggested that JAK3 was the target gene of miR-4486. qRT-PCR and WB proved that miR-4486/JAK3 axis inhibit the activation of JAK3/STAT3 pathway, and JAK3 overexpression can partly reverse this. As shown by CCK-8 and flow cytometry, miR-4486 overexpression decreased viability and stimulated apoptosis of SGC-7901/DDP cells. However, JAK3 overexpression can also partly revert this. miR-4486 overexpression could decrease viability and improve apoptosis of SGC-7901/DDP cells to revert its cisplatin-resistance, and the mechanism may be related to JAK3/STAT3 signalling pathway.
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Affiliation(s)
- Caijin Zhou
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Linxia Chen
- Department of Operating Room, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Rihong Chen
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Feipeng Xu
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Zhe Huang
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Renwei Huang
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Weiwei Wang
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Qingwen Xu
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
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4
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Zangouei AS, Moghbeli M. MicroRNAs as the critical regulators of cisplatin resistance in gastric tumor cells. Genes Environ 2021; 43:21. [PMID: 34099061 PMCID: PMC8182944 DOI: 10.1186/s41021-021-00192-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/24/2021] [Indexed: 12/13/2022] Open
Abstract
Combined chemotherapeutic treatment is the method of choice for advanced and metastatic gastric tumors. However, resistance to chemotherapeutic agents is one of the main challenges for the efficient gastric cancer (GC) treatment. Cisplatin (CDDP) is used as an important regimen of chemotherapy for GC which induces cytotoxicity by interfering with DNA replication in cancer cells and inducing their apoptosis. Majority of patients experience cisplatin-resistance which is correlated with tumor metastasis and relapse. Moreover, prolonged and high-dose cisplatin administrations cause serious side effects such as nephrotoxicity, ototoxicity, and anemia. Since, there is a high rate of recurrence after CDDP treatment in GC patients; it is required to clarify the molecular mechanisms associated with CDDP resistance to introduce novel therapeutic methods. There are various cell and molecular processes associated with multidrug resistance (MDR) including drug efflux, detoxification, DNA repair ability, apoptosis alteration, signaling pathways, and epithelial-mesenchymal transition (EMT). MicroRNAs are a class of endogenous non-coding RNAs involved in chemo resistance of GC cells through regulation of all of the MDR mechanisms. In present review we have summarized all of the miRNAs associated with cisplatin resistance based on their target genes and molecular mechanisms in gastric tumor cells. This review paves the way of introducing a miRNA-based panel of prognostic markers to improve the efficacy of chemotherapy and clinical outcomes in GC patients. It was observed that miRNAs are mainly involved in cisplatin response of gastric tumor cells via regulation of signaling pathways, autophagy, and apoptosis.
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Affiliation(s)
- Amir Sadra Zangouei
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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5
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Luo D, Yang Q, Wang H, Tan M, Zou Y, Liu J. A predictive model for assessing prognostic risks in gastric cancer patients using gene expression and methylation data. BMC Med Genomics 2021; 14:14. [PMID: 33407483 PMCID: PMC7789242 DOI: 10.1186/s12920-020-00856-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 12/10/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The role(s) of epigenetic reprogramming in gastric cancer (GC) remain obscure. This study was designed to identify methylated gene markers with prognostic potential for GC. METHODS Five datasets containing gene expression and methylation profiles from GC samples were collected from the GEO database, and subjected to meta-analysis. All five datasets were subjected to quality control and then differentially expressed genes (DEGs) and differentially expressed methylation genes (DEMGs) were selected using MetaDE. Correlations between gene expression and methylation status were analysed using Pearson coefficient correlation. Then, enrichment analyses were conducted to identify signature genes that were significantly different at both the gene expression and methylation levels. Cox regression analyses were performed to identify clinical factors and these were combined with the signature genes to create a prognosis-related predictive model. This model was then evaluated for predictive accuracy and then validated using a validation dataset. RESULTS This study identified 1565 DEGs and 3754 DEMGs in total. Of these, 369 were differentially expressed at both the gene and methylation levels. We identified 12 signature genes including VEGFC, FBP1, NR3C1, NFE2L2, and DFNA5 which were combined with the clinical data to produce a novel prognostic model for GC. This model could effectively split GC patients into two groups, high- and low-risk with these observations being confirmed in the validation dataset. CONCLUSION The differential methylation of the 12 signature genes, including VEGFC, FBP1, NR3C1, NFE2L2, and DFNA5, identified in this study may help to produce a functional predictive model for evaluating GC prognosis in clinical samples.
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Affiliation(s)
- Dan Luo
- Department of General Surgery, Chengdu Fifth People’s Hospital, 33 Mashi St, Chengdu, 610000 Sichuan China
| | - QingLing Yang
- Department of Pulmonary and Critical Care Medicine, Chengdu Fifth People’s Hospital, 33 Mashi St, Chengdu, 610000 Sichuan China
| | - HaiBo Wang
- Department of General Surgery, Chengdu Fifth People’s Hospital, 33 Mashi St, Chengdu, 610000 Sichuan China
| | - Mao Tan
- Department of General Surgery, Chengdu Fifth People’s Hospital, 33 Mashi St, Chengdu, 610000 Sichuan China
| | - YanLei Zou
- Department of General Surgery, Chengdu Fifth People’s Hospital, 33 Mashi St, Chengdu, 610000 Sichuan China
| | - Jian Liu
- Department of General Surgery, Chengdu Fifth People’s Hospital, 33 Mashi St, Chengdu, 610000 Sichuan China
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6
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Non-coding RNAs underlying chemoresistance in gastric cancer. Cell Oncol (Dordr) 2020; 43:961-988. [PMID: 32495294 DOI: 10.1007/s13402-020-00528-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 04/17/2020] [Accepted: 04/24/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is a major health issue in the Western world. Current clinical imperatives for this disease include the identification of more effective biomarkers to detect GC at early stages and enhance the prevention and treatment of metastatic and chemoresistant GC. The advent of non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long-non coding RNAs (lncRNAs), has led to a better understanding of the mechanisms by which GC cells acquire features of therapy resistance. ncRNAs play critical roles in normal physiology, but their dysregulation has been detected in a variety of cancers, including GC. A subset of ncRNAs is GC-specific, implying their potential application as biomarkers and/or therapeutic targets. Hence, evaluating the specific functions of ncRNAs will help to expand novel treatment options for GC. CONCLUSIONS In this review, we summarize some of the well-known ncRNAs that play a role in the development and progression of GC. We also review the application of such ncRNAs in clinical diagnostics and trials as potential biomarkers. Obviously, a deeper understanding of the biology and function of ncRNAs underlying chemoresistance can broaden horizons toward the development of personalized therapy against GC.
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7
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Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5103272. [PMID: 32855967 PMCID: PMC7443216 DOI: 10.1155/2020/5103272] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 06/18/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022]
Abstract
Human gastric cancer is one of the most common malignant tumors with a poor prognosis. Cisplatin (CDDP) is a well-known first-line chemotherapeutic drug. Acquired resistance retards the clinical application of CDDP in gastric cancer. In this study, circular RNA circ_0026359 was demonstrated to be overexpressed in gastric cancer tissues/cells compared with normal gastric tissues/cells and was overexpressed in CDDP-resistant gastric cancer tissues/cells compared with CDDP-sensitive gastric cancer tissues/cells. High levels of circ_0026359 were associated with low overall survival (OS) and relapse-free survival (RFS) rates in gastric cancer patients. circ_0026359 was examined to promote CDDP resistance in gastric cancer cells. circ_0026359 directly interacted and negatively regulated miR-1200. POLD4 was a direct target of miR-1200. miR-1200/POLD4 pathway mediated the promoting role of circ_0026359 in CDDP resistance of gastric cancer. circ_0026359 could be used as a potential target for CDDP-resistant gastric cancer therapy.
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8
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Wang CA, Chang IH, Hou PC, Tai YJ, Li WN, Hsu PL, Wu SR, Chiu WT, Li CF, Shan YS, Tsai SJ. DUSP2 regulates extracellular vesicle-VEGF-C secretion and pancreatic cancer early dissemination. J Extracell Vesicles 2020; 9:1746529. [PMID: 32341770 PMCID: PMC7170376 DOI: 10.1080/20013078.2020.1746529] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 02/17/2020] [Accepted: 03/13/2020] [Indexed: 12/21/2022] Open
Abstract
Early dissemination is a unique characteristic and a detrimental process of pancreatic ductal adenocarcinoma (PDAC); however, the underlying mechanism remains largely unknown. Here, we investigate the role of dual-specificity phosphatase-2 (DUSP2)-vascular endothelial growth factor-C (VEGF-C) axis in mediating PDAC lymphangiogenesis and lymphovascular invasion. Expression of DUSP2 is greatly suppressed in PDAC, which results in increased aberrant expression of extracellular vesicle (EV)-associated VEGF-C secretion. EV-VEGF-C exerts paracrine effects on lymphatic endothelial cells and autocrine effects on cancer cells, resulting in the lymphovascular invasion of cancer cells. Tissue-specific knockout of Dusp2 in mouse pancreas recapitulates PDAC phenotype and lymphovascular invasion. Mechanistically, loss-of-DUSP2 enhances proprotein convertase activity and vesicle trafficking to promote the release of the mature form of EV-VEGF-C. Collectively, these findings represent a conceptual advance in understanding pancreatic cancer lymphovascular invasion and suggest that loss-of-DUSP2-mediated VEGF-C processing may play important roles in early dissemination of pancreatic cancer. Abbreviations: DUSP2: dual-specificity phosphatase-2; VEGF-C: vascular endothelial growth factor-C; EV: extracellular vesicles; PDAC: pancreatic ductal adenocarcinoma; KD: knockdown
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Affiliation(s)
- Chu-An Wang
- Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - I-Heng Chang
- Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Livestock Research Institute, Council of Agriculture, Tainan, Taiwan
| | - Pei-Chi Hou
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Jing Tai
- Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wan-Ning Li
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Pei-Ling Hsu
- Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shang-Rung Wu
- Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Tai Chiu
- Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Chien-Feng Li
- Department of Pathology, Chi-Mei Foundational Medical Center, Tainan, Taiwan.,National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Yan-Shen Shan
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Surgery, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shaw-Jenq Tsai
- Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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9
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Wei L, Sun J, Zhang N, Zheng Y, Wang X, Lv L, Liu J, Xu Y, Shen Y, Yang M. Noncoding RNAs in gastric cancer: implications for drug resistance. Mol Cancer 2020; 19:62. [PMID: 32192494 PMCID: PMC7081551 DOI: 10.1186/s12943-020-01185-7] [Citation(s) in RCA: 324] [Impact Index Per Article: 64.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Accepted: 03/12/2020] [Indexed: 12/18/2022] Open
Abstract
Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.
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Affiliation(s)
- Ling Wei
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Jujie Sun
- Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Nasha Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Yan Zheng
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Xingwu Wang
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Liyan Lv
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Jiandong Liu
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Yeyang Xu
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Yue Shen
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Ming Yang
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China.
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10
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Saitoh Y, Umezu T, Imanishi S, Asano M, Yoshizawa S, Katagiri S, Suguro T, Fujimoto H, Akahane D, Kobayashi-Kawana C, Ohyashiki JH, Ohyashiki K. Downregulation of extracellular vesicle microRNA-101 derived from bone marrow mesenchymal stromal cells in myelodysplastic syndrome with disease progression. Oncol Lett 2020; 19:2053-2061. [PMID: 32194702 PMCID: PMC7038917 DOI: 10.3892/ol.2020.11282] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 11/11/2019] [Indexed: 12/21/2022] Open
Abstract
To evaluate the mechanism underlying the communication between myeloid malignant and bone marrow (BM) microenvironment cells in disease progression, the current study established BM mesenchymal stromal cells (MSCs) and assessed extracellular vesicle (EV) microRNA (miR) expression in 22 patients with myelodysplastic syndrome (MDS) and 7 patients with acute myeloid leukemia and myelodysplasia-related changes (AML/MRC). Patients with MDS were separated into two categories based on the revised International Prognostic Scoring System (IPSS-R), and EV-miR expression in BM-MSCs was evaluated using a TaqMan low-density array. The selected miRs were evaluated using reverse transcription-quantitative PCR. The current study demonstrated that the expression of BM-MSC-derived EV-miR was heterogenous and based on MDS severity, the expression of EV-miR-101 was lower in high-risk group and patients with AML/MRC compared with the control and low-risk groups. This reversibly correlated with BM blast percentage, with which the cellular miR-101 from BM-MSCs or serum EV-miR-101 expression exhibited no association. Database analyses indicated that miR-101 negatively regulated cell proliferation and epigenetic gene expression. The downregulation of BM-MSC-derived EV-miR-101 may be associated with cell-to-cell communication and may accelerate the malignant process in MDS cells.
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Affiliation(s)
- Yuu Saitoh
- Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan
- Department of Hematology, Shizuoka General Hospital, Shizuoka 420-8527, Japan
| | - Tomohiro Umezu
- Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan
- Department of Molecular Pathology, Tokyo Medical University, Tokyo 160-8402, Japan
| | - Satoshi Imanishi
- Institute of Medical Sciences, Tokyo Medical University, Tokyo 160-0023, Japan
| | - Michiyo Asano
- Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan
| | | | - Seiichiro Katagiri
- Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan
| | - Tamiko Suguro
- Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan
| | - Hiroaki Fujimoto
- Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan
| | - Daigo Akahane
- Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan
| | | | - Junko H. Ohyashiki
- Institute of Medical Sciences, Tokyo Medical University, Tokyo 160-0023, Japan
- Department of Advanced Cellular Therapy, Tokyo Medical University, Tokyo 160-0023, Japan
| | - Kazuma Ohyashiki
- Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan
- Department of Advanced Cellular Therapy, Tokyo Medical University, Tokyo 160-0023, Japan
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11
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Luo YJ, Huang QM, Ren Y, Liu ZL, Xu CF, Wang H, Xiao JW. Non-coding RNA in drug resistance of gastric cancer. World J Gastrointest Oncol 2019; 11:957-970. [PMID: 31798777 PMCID: PMC6883183 DOI: 10.4251/wjgo.v11.i11.957] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 09/21/2019] [Accepted: 10/03/2019] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. The poorly prognosis and survival of GC are due to diagnose in an advanced, non-curable stage and with a limited response to chemotherapy. The acquisition of drug resistance accounts for the majority of therapy failure of chemotherapy in GC patients. Although the mechanisms of anticancer drug resistance have been broadly studied, the regulation of these mechanisms has not been completely understood. Accumulating evidence has recently highlighted the role of non-coding RNAs (ncRNAs), including long non-coding RNAs and microRNAs, in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of GC. We review the literature on ncRNAs in drug resistance of GC. This review summarizes the current knowledge about the ncRNAs’ characteristics, their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant GC.
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Affiliation(s)
- Ya-Jun Luo
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Qing-Mei Huang
- Department of Oncology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Yan Ren
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Zi-Lin Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Cheng-Fei Xu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Hao Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Jiang-Wei Xiao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
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12
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Chen C, Tang X, Liu Y, Zhu J, Liu J. Induction/reversal of drug resistance in gastric cancer by non-coding RNAs (Review). Int J Oncol 2019; 54:1511-1524. [PMID: 30896792 PMCID: PMC6438417 DOI: 10.3892/ijo.2019.4751] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 02/21/2019] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer (GC) is one of the most prevalent and malignant types of cancer worldwide. In China, it is the second most common type of cancer and the malignancy with the highest incidence and mortality rate. Chemotherapy for GC is not always effective due to the development of drug resistance. Drug resistance, which is frequently observed in GC, undermines the success rate of chemotherapy and the survival of patients with GC. The dysregulation of non‑coding RNAs (ncRNAs), primarily microRNAs (miRNAs or miRs) and long non‑coding RNAs (lncRNAs), is involved in the development of GC drug resistance via numerous mechanisms. These mechanisms contribute to the involvement of a large and complex network of ncRNAs in drug resistance. In this review, we focus on and summarize the latest research on the specific mechanisms of action of miRNAs and lncRNAs that modulate drug resistance in GC. In addition, we discuss future prospects and clinical applications of ncRNAs as potential targeted therapies against the chemoresistance of GC.
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Affiliation(s)
- Chao Chen
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Xiaohuan Tang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Yuanda Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Jiaming Zhu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Jingjing Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
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13
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Tang C, Cheng X, Yu S, Wang Y, Hou J, Li Q, Shen Z, Liu T, Cui Y. Platelet-to-lymphocyte ratio and lymphocyte-to-white blood cell ratio predict the efficacy of neoadjuvant chemotherapy and the prognosis of locally advanced gastric cancer patients treated with the oxaliplatin and capecitabine regimen. Onco Targets Ther 2018; 11:7061-7075. [PMID: 30410363 PMCID: PMC6200072 DOI: 10.2147/ott.s176768] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Many studies have discussed the relationship between routine blood parameters and the prognosis of gastric cancer patients; however, few studies focused on the association of routine blood parameters with the efficacy of neoadjuvant chemotherapy (NAC). Patients and methods We retrospectively collected routine blood parameters and other clinicopathological data of 104 patients with locally advanced gastric cancer (LAGC) who received the oxaliplatin and capecitabine regimen as NAC from June 2010 to March 2016. The objective response rate (ORR), pathological remission rate (pRR), overall survival (OS), and time to recurrence (TTR) were analyzed through different statistical methods, such as Chi-squared test, log-rank test, logistic regression, and Cox regression. Results In the multivariate analysis, a high platelet-to-lymphocyte ratio (PLR) (≥130.7) predicted a low ORR (OR =5.927, 95% CI: 2.184–16.089) and a low pRR (OR =8.343, 95% CI: 2.178–31.962), while a high lymphocyte-to-white blood cell ratio (LWR) (≥0.228) independently predicted a high ORR (OR =0.118, 95% CI: 0.031–0.448) and a high pRR (OR =0.096, 95% CI: 0.021–0.426). High lymphocyte level (≥1.750×109/L) was an independent predictor of long OS (HR =0.428, 95% CI: 0.190–0.964) and long TTR (HR =0.328, 95% CI: 0.156–0.690). High monocyte level (≥0.215×109/L) was associated with a high pRR (OR =0.072, 95% CI: 0.008–0.636) and a long OS (HR = 0.506, 95% CI: 0.257–0.997). Conclusion In patients with LAGC treated with the oxaliplatin and capecitabine regimen as NAC, a low PLR (<130.7) and a high LWR (≥0.228) independently predicted a high ORR and pRR. High monocyte level (≥0.215×109/L) was an independent predictor for a high pRR and long OS, while patients with high lymphocyte level (≥1.750×109/L) tended to have a long OS and TTR.
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Affiliation(s)
- Cheng Tang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; ;
| | - Xi Cheng
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; ;
| | - Shan Yu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; ;
| | - Yan Wang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; ;
| | - Jun Hou
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qian Li
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; ;
| | - Zhenbin Shen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tianshu Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; ;
| | - Yuehong Cui
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; ;
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14
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Raimondi A, Nichetti F, Peverelli G, Di Bartolomeo M, De Braud F, Pietrantonio F. Genomic markers of resistance to targeted treatments in gastric cancer: potential new treatment strategies. Pharmacogenomics 2018; 19:1047-1068. [PMID: 30041572 DOI: 10.2217/pgs-2018-0077] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer is a highly heterogeneous disease, displaying a complex genomic landscape and an unfavorable outcome with standard therapies. Based on distinctive genomic alterations, novel targeted agents have been developed with the aim of personalizing treatments and improving patient outcome. However, a subgroup of patients is primarily treatment-resistant, and even in the initially sensitive population, secondary resistance emerges, thus limiting therapeutic benefit. In this review, we summarize the clinical data about standard targeted agents in gastric cancer, specifically anti-HER2 treatments and antivascular therapies. We also illustrate the available evidence regarding molecular mechanisms of resistance to these agents and we discuss potential strategies for new targeted treatments that could overcome such resistance.
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Affiliation(s)
- Alessandra Raimondi
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Federico Nichetti
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giorgia Peverelli
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maria Di Bartolomeo
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo De Braud
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.,Department of Oncology & Hemato-oncology, University of Milan, Italy
| | - Filippo Pietrantonio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.,Department of Oncology & Hemato-oncology, University of Milan, Italy
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15
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Koduru SV, Leberfinger AN, Kawasawa YI, Mahajan M, Gusani NJ, Sanyal AJ, Ravnic DJ. Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. Sci Rep 2018; 8:7967. [PMID: 29789629 PMCID: PMC5964116 DOI: 10.1038/s41598-018-26360-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 05/10/2018] [Indexed: 12/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) was the fifth leading cause of cancer death in men and eighth leading cause of death in women in the United States in 2017. In our study, we sought to identify sncRNAs in various stages of development of HCC. We obtained publicly available small RNA-seq data derived from patients with cirrhosis (n = 14), low-grade dysplastic nodules (LGDN, n = 9), high grade dysplastic nodules (HGDN, n = 6), early hepatocellular carcinoma (eHCC, n = 6), and advanced hepatocellular carcinoma (HCC, n = 20), along with healthy liver tissue samples (n = 9). All samples were analyzed for various types of non-coding RNAs using PartekFlow software. We remapped small RNA-seq to miRBase to obtain differential expressions of miRNAs and found 87 in cirrhosis, 106 in LGDN, 59 in HGDN, 80 in eHCC, and 133 in HCC. Pathway analysis of miRNAs obtained from diseased samples compared to normal samples showed signaling pathways in the microRNA dependent EMT, CD44, and others. Additionally, we analyzed the data sets for piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. We validated the in silico data using human HCC samples with NanoString miRNA global expression. Our results suggest that publically available data is a valuable resource for sncRNA identification in HCC progression (FDR set to <0.05 for all samples) and that a data mining approach is useful for biomarker development.
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Affiliation(s)
- Srinivas V Koduru
- Division of Plastic Surgery, Department of Surgery, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
| | - Ashley N Leberfinger
- Division of Plastic Surgery, Department of Surgery, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
| | - Yuka I Kawasawa
- Department of Pharmacology, Department of Biochemistry & Molecular Biology, and Institute for Personalized Medicine, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
| | - Milind Mahajan
- Genomics Facility, Department of Genetics and Genomics Sciences, Icahn School of Medicine, Mount Sinai, 1425 Madison Ave, New York, NY, 10029, USA
| | - Niraj J Gusani
- Program for Liver, Pancreas, & Foregut Tumors, Department of Surgery, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, 1201 E Marshall St, Richmond, VA, 23298, USA
| | - Dino J Ravnic
- Division of Plastic Surgery, Department of Surgery, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
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16
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Wei F, Jiang X, Gao HY, Gao SH. Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo. Int J Oncol 2017; 51:1383-1394. [PMID: 29048624 PMCID: PMC5642394 DOI: 10.3892/ijo.2017.4134] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 07/20/2017] [Indexed: 02/04/2023] Open
Abstract
Gastric cancer is reported as one of the leading factors resulting in tumor-related death worldwide. However, the therapies to suppress gastric cancer are still limited and the emergence of drug resistance makes it necessary to develop new and effective anticancer drugs and combinational chemotherapy schemes. Liquiritin (LIQ) is a major constituent of Glycyrrhiza Radix, exhibiting various pharmacological activities, including anticancer. In this study, we investigated the role of LIQ in human gastric cancer cells with cisplatin (DDP) resistance. The findings suggested that LIQ, when applied in single therapy, could moderately inhibit the proliferation and migration of DDP-resistant gastric cancer cells, SGC7901/DDP. DDP and LIQ in combination induced G0/G1 cell cycle arrest to suppress the proliferation of gastric cancer cells, which were associated with the decrease of cyclin D1, cyclin A and cyclin-dependent kinase 4 (CDK4) and increase of p53 and p21. In addition, LIQ combined with DDP significantly induce apoptosis and autophagy both in vitro and in vivo through enhancing cleavage of caspase-8/-9/-3 and PARP, as well as LC3B and Beclin 1 expression. Significantly, the two drugs, when used in combination, prevented gastric cancer cell xenografts in nude mice in vivo. Together, the results revealed that application of DDP and LIQ in combination possessed a potential value against the growth of human gastric cancer with DDP resistance.
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Affiliation(s)
- Feng Wei
- Department of Hepatobiliary and Pancreas Surgery, First Hospital of Jilin University
| | - Xin Jiang
- Department of Biochemistry, Basic College of Medicine, Jilin University
| | - Hao-Yue Gao
- Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Shuo-Hui Gao
- Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University
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17
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Choudhry H, Zamzami MA, Omran Z, Wu W, Mousli M, Bronner C, Alhosin M. Targeting microRNA/UHRF1 pathways as a novel strategy for cancer therapy. Oncol Lett 2017; 15:3-10. [PMID: 29285183 PMCID: PMC5738699 DOI: 10.3892/ol.2017.7290] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 09/22/2017] [Indexed: 12/11/2022] Open
Abstract
Ubiquitin-like containing plant homeodomain and RING finger domains 1 (UHRF1) is an anti-apoptotic protein involved in the silencing of several tumor suppressor genes (TSGs) through epigenetic modifications including DNA methylation and histone post-translational alterations, and also epigenetic-independent mechanisms. UHRF1 overexpression is observed in a number of solid tumors and hematological malignancies, and is considered a primary mechanism in inhibiting apoptosis. UHRF1 exerts its inhibitory activity on TSGs by binding to functional domains and therefore influences several epigenetic actors including DNA methyltransferase, histone deacetylase 1, histone acetyltransferase Tat-interacting protein 60 and histone methyltransferases G9a and Suv39H1. UHRF1 is considered to control a large macromolecular protein complex termed epigenetic code replication machinery, in order to maintain epigenetic silencing of TSGs during cell division, thus enabling cancer cells to escape apoptosis. MicroRNAs (miRNAs) are able to regulate the expression of its target gene by functioning as either an oncogene or a tumor suppressor. In the present review, the role of tumor suppressive miRNAs in the regulation of UHRF1, and the importance of targeting the microRNA/UHRF1 pathways in order to induce the reactivation of silenced TSGs and subsequent apoptosis are discussed.
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Affiliation(s)
- Hani Choudhry
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Cancer Metabolism and Epigenetic Unit, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Mazin A Zamzami
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Cancer Metabolism and Epigenetic Unit, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Ziad Omran
- College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Wei Wu
- Department of Medicine, University of California, San Francisco, CA 94143, USA
| | - Marc Mousli
- Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, 67401 Illkirch Cedex, France
| | - Christian Bronner
- Institute of Genetics and Molecular and Cellular Biology (IGBMC), National Institute of Health and Medical Research U964, National Center for Scientific Research UMR7104, University of Strasbourg, 67404 Illkirch Cedex, France
| | - Mahmoud Alhosin
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Cancer Metabolism and Epigenetic Unit, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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18
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Yang W, Ma J, Zhou W, Cao B, Zhou X, Yang Z, Zhang H, Zhao Q, Fan D, Hong L. Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer. Expert Opin Ther Targets 2017; 21:1063-1075. [PMID: 28994330 DOI: 10.1080/14728222.2017.1389900] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.
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Affiliation(s)
- Wanli Yang
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Jiaojiao Ma
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Wei Zhou
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Bo Cao
- b The First Brigade of Student , Fourth Military Medical University , Xi'an , China
| | - Xin Zhou
- b The First Brigade of Student , Fourth Military Medical University , Xi'an , China
| | - Zhiping Yang
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Hongwei Zhang
- c Department of Digestive Surgery, Xijing Hospital , Fourth Military Medical University , Xi'an , China
| | - Qingchuan Zhao
- c Department of Digestive Surgery, Xijing Hospital , Fourth Military Medical University , Xi'an , China
| | | | - Liu Hong
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
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19
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Ma Y, Luo W, Bunch BL, Pratt RN, Trump DL, Johnson CS. 1,25D 3 differentially suppresses bladder cancer cell migration and invasion through the induction of miR-101-3p. Oncotarget 2017; 8:60080-60093. [PMID: 28947955 PMCID: PMC5601123 DOI: 10.18632/oncotarget.19629] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 07/19/2017] [Indexed: 12/17/2022] Open
Abstract
Metastasis is the major cause of bladder cancer death. 1,25D3, the active metabolite of vitamin D, has shown anti-metastasis activity in several cancer model systems. However, the role of 1,25D3 in migration and invasion in bladder cancer is unknown. To investigate whether 1,25D3 affects migration and invasion, four human bladder cell lines with different reported invasiveness were selected: low-invasive T24 and 253J cells and highly invasive 253J-BV and TCCSUP cells. All of the four bladder cancer cells express endogenous and inducible vitamin D receptor (VDR) as examined by immunoblot analysis. 1,25D3 had no effect on the proliferation of bladder cancer cells as assessed by MTT assay. In contrast, 1,25D3 suppressed migration and invasion in the more invasive 253J-BV and TCCSUP cells, but not in the low-invasive 253J and T24 cells using "wound" healing, chemotactic migration and Matrigel-based invasion assays. 1,25D3 promoted the expression of miR-101-3p and miR-126-3p in 253J-BV cells as examined by qRT-PCR. miR-101-3p inhibitor partially abrogated and pre-miR-101-3p further suppressed the inhibition of 1,25D3 on migration and invasion in 253J-BV cells. Further, 1,25D3 enhanced VDR recruitment to the promoter region of miR-101-3p using ChIP-qPCR assay. 1,25D3 enhanced the promoter activity of miR-101-3p as evaluated by luciferase reporter assay. Taken together, 1,25D3 suppresses bladder cancer cell migration and invasion in two invasive/migration competent lines but not in two less invasive/motile lines, which is partially through the induction of miR-101-3p expression at the transcriptional level.
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Affiliation(s)
- Yingyu Ma
- Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA
| | - Wei Luo
- Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA
| | - Brittany L. Bunch
- Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA
| | - Rachel N. Pratt
- Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA
| | | | - Candace S. Johnson
- Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA
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20
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Zhang Z, Zhao J, Pang Q, Wang A, Chen M, Wei X. An in vitro study on the effects of the combination of salinomycin with cisplatin on human gastric cancer cells. Mol Med Rep 2017. [PMID: 28627601 PMCID: PMC5561897 DOI: 10.3892/mmr.2017.6731] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
The present study aimed to investigate the anticancer effects of cisplatin (DDP) combined with salinomycin (SAL) on the gastric cancer cell line SGC-7901, as well as to explore the mechanisms underlying their actions. An MTT assay was used to evaluate the inhibitory effects of SAL, DDP and their combination on gastric cancer cell proliferation. Morphological alterations of cancer cells following treatment were observed under an inverted phase-contrast microscope and a fluorescence microscope. Cell cycle progression and apoptosis were analyzed using flow cytometry. The expression of nuclear factor (NF)-κB p65 and Fas protein ligand (L) in cancer cells was assessed using immunocytochemistry. The present results demonstrated that the combination of SAL and DDP significantly inhibited the proliferation (P<0.05) and altered the morphological characteristics of SGC-7901 cells, thus suggesting that SAL may enhance the susceptibility of gastric cancer cells to DDP. In addition, treatment with a combination of SAL and DDP resulted in S phase-arrest and increased the apoptotic rate of SGC-7901 cells. Furthermore, marked FasL upregulation and NF-κB p65 downregulation were observed in cancer cells treated with the combination of SAL and DDP. The results of the present study demonstrated that the combination of SAL and DDP induced the apoptosis of human gastric cancer cells, and suggested that the underlying mechanism may involve the upregulation of FasL and downregulation of NF-κB p65.
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Affiliation(s)
- Zuwen Zhang
- Medical College, Yan'an University, Yanan, Shaanxi 716000, P.R. China
| | - Jumei Zhao
- Medical College, Yan'an University, Yanan, Shaanxi 716000, P.R. China
| | - Qiuxia Pang
- Medical College, Yan'an University, Yanan, Shaanxi 716000, P.R. China
| | - Aihong Wang
- Medical College, Yan'an University, Yanan, Shaanxi 716000, P.R. China
| | - Meini Chen
- Medical College, Yan'an University, Yanan, Shaanxi 716000, P.R. China
| | - Xiaoli Wei
- Medical College, Yan'an University, Yanan, Shaanxi 716000, P.R. China
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21
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Biersack B. Interactions between anticancer active platinum complexes and non-coding RNAs/microRNAs. Noncoding RNA Res 2017; 2:1-17. [PMID: 30159416 PMCID: PMC6096430 DOI: 10.1016/j.ncrna.2016.10.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 10/07/2016] [Accepted: 10/07/2016] [Indexed: 12/13/2022] Open
Abstract
Platinum(II) complexes such as cisplatin, carboplatin and oxaliplatin are clinically approved for the therapy of various solid tumors. Challenging pathogenic properties of cancer cells and the response of cancers towards platinum-based drugs are strongly influenced by non-coding small RNA molecules, the microRNAs (miRNAs). Both increased platinum activity and formation of tumor resistance towards platinum drugs are controlled by miRNAs. This review gives an overview of the interactions between platinum-based drugs and miRNAs, and their influence on platinum activity in various cancer types is discussed.
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Key Words
- 5-FU, 5-fluorouracil
- Anticancer drugs
- CBDCA, cyclobutane-1,1-dicarboxylate
- Carboplatin
- Cisplatin
- DACH, 1,2-diaminocyclohexane
- DDP, cisplatin
- EGCG, (−)-epigallocatechin-3-gallate
- EOX, epirubicin/oxaliplatin/xeloda
- FOLFOX, folinate/5-FU/oxaliplatin
- GC, gemcitabine/cisplatin, gastric cancer
- LNA, locked nucleic acid
- MVAC, methotrexate/vinblastine/adriamycin/cisplatin
- MicroRNA
- Oxaliplatin
- Platinum complexes
- XELOX, xeloda/oxaliplatin
- dTTP, deoxythymidine triphosphate
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22
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Abstract
Drug resistance of gastric cancer cells is one of the main reasons that lead to failure of chemotherapy in gastric cancer. Gastric cancer cells can be resistant to chemotherapeutic drugs and targeted drugs, which leads to poor therapeutic effects. Although the mechanisms of drug resistance of gastric cancer cells have long been investigated, no effective drug that can reverse the drug resistance of gastric cancer cells has been found. Therefore, it is important to reverse the drug resistance of gastric cancer cells to improve the prognosis of gastric cancer. In this paper, we review the mechanisms of drug resistance of gastric cancer cells to chemotherapeutic drugs and targeted drugs, summarize current situation for research of drug resistance of gastric cancer cells, and discuss the future development direction in this field.
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